Management of Asthma Exacerbations
Authors: Kristina L. Simeonsson, MD, MSPH, Assistant Professor of Pediatrics, Brody School of Medicine at East Carolina University, Greenville, NC; Roytesa Savage, MD, Assistant Professor of Pediatrics, Brody School of Medicine at East Carolina University, Greenville, NC.
Peer Reviewer: Ghazala Q. Sharieff, MD, FACEP, FAAEM, FAAP, Division Director, San Diego Rady Children's Hospital Emergency Care Center, San Diego, CA; Director of Pediatric Emergency Medicine, Palomar-Pomerado Health System/California Emergency Physicians.
Introduction
Asthma is the most common chronic childhood illness; it is estimated that it currently affects 6 million children in the United States. The prevalence of asthma in children is higher than in adults 8.5% compared to 6.7% respectively.1 Prevalence of asthma is higher in some minority children as well. Data from the recent National Health Interview Survey (2001–2005) found the prevalence of asthma for black children and American Indian/Alaskan Native children to be 13%.3
In 2005, an estimated 4.2% of people in the United States had at least one asthma attack in the previous year. Among those who currently had asthma, over half had at least one asthma attack in the previous year.1 Similar to overall prevalence for asthma, the asthma attack prevalence decreased with increasing age: 5.2% of children had an asthma attack in the previous year compared to 3.9% of adults.1
Asthma results in a large number of acute care visits; it accounts for 2% of all visits to the emergency department (ED), with an annual average of about 1.8 million visits.4,5 For children younger than 10 years of age, the rate of ED visits for asthma is 13 visits per 1,000 population, higher than for the general population, which has a rate of six visits per 1,000 population.5 In 2004, there were 198,000 hospitalizations, 754,000 ED visits, and seven million outpatient visits for asthma in children younger than age 18.1
The Healthy People 2010 objectives for asthma specified a reduction in the rate of ED visits for young children to less than eight visits per 1,000 population.6 The objectives also included an increase in the proportion of persons provided appropriate asthma care in accordance with the National Asthma Education and Prevention Program (NAEPP) guidelines.7 The most recent version of these clinical practice guidelines was released in 2007 and included new information on categorizing the severity of asthma, pharmacologic management, and the management of asthma exacerbations.
Etiology
The cause of asthma is a combination of host factors and environmental exposures. There is clearly a genetic predisposition to asthma; parental history of asthma is one of the strongest predictors for the development of asthma.8,9 Other host factors that are significant in early childhood asthma include race,3,4,10 male gender,4,9,10 and prematurity.11 Regardless of race, children born at or before 32 weeks gestation are at increased risk for childhood asthma.11
Allergy or allergic sensitization in young children has emerged as one of the major risk factors for asthma; it is also thought to be linked to the persistence and severity of asthma.12 The initial presentation of asthma is thought to be the culmination of the "allergic march" that begins early in life and includes three stages: food allergies and dermatitis, allergic rhinoconjuctivitis, and asthma.13
Asthma can be thought of as an exaggerated response to environmental stimuli, often categorized as allergic and nonallergic. Allergic stimuli include dust mites, pollen, mold, environmental tobacco smoke, and animal dander. Nonallergic triggers include exercise, cold air, air pollution, and infectious agents. Each patient with asthma will have specific triggers that can set off an exacerbation. Respiratory viral infections are the most frequent triggers in childhood asthma; one study of children 9–11 years of age found that more than 80% of asthma exacerbations were caused by respiratory viruses.14
Pathophysiology
Asthma is a complex chronic inflammatory condition of the airways marked by episodic and reversible airflow obstruction. Inflammation is the underlying abnormality which leads to airway obstruction, and the severity of episodes depends on the degree of obstruction. Although the definitive cause of the inflammatory response in asthma has not been completely identified, the development of immunoglobulin type E (IgE)-mediated responses to common allergens is one identifiable event that leads to asthma. In individuals with asthma, this IgE-mediated response activates many of the inflammatory cells involved in the response. 15,16
Airway obstruction is attributable to three distinct processes: bronchoconstriction, airway hyperresponsiveness, and airway edema.15 Smooth muscle in the lungs constricts in response to chemical mediators released from mast cells; this bronchoconstriction results in narrowing of the airways.18 Airway hyperresponsiveness is an overexaggerated response to a variety of stimuli, which leads to additional narrowing. Airway edema is a late response in the pathogenesis of asthma symptoms; edema, in combination with an increase in mucus production, further limits airflow. The end process results in airway obstruction with the clinical picture of difficulty breathing, air trapping, and lung hyperinflation.7,16
Remodeling of the airway occurs after repeated episodes of airway inflammation. Longstanding inflammatory changes cause smooth muscle hypertrophy, mucus hypersecretion, injury to epithelial cells, sub-basement fibrosis, and angiogenesis.7 Airway remodeling can lead to chronic airway obstruction that is irreversible. Irreversible airway damage can in turn lead to more severe exacerbations.17,19
Differential Diagnosis
Although cough and wheezing are common features of asthma, they are not pathognomonic. By 6 years of age, almost 50% of children will have had at least one episode of wheezing.10 The differential diagnosis of asthma includes a number of disease processes, including cardiopulmonary and gastrointestinal diseases as well as anatomic abnormalities. While asthma remains the most common cause of recurrent episodes of coughing, wheezing, and shortness of breath in children, the following section will review some of the more common misdiagnoses of asthma as well as diseases that can complicate asthma. The ED physician should be familiar with these diagnoses, especially in patients who present with their first episode of wheezing. ED physicians should also consider these diagnoses in patients who do not respond as expected to standard asthma therapy.
Anatomical Obstruction. A child presenting to the ED for an initial episode of wheezing without a family history of asthma needs to be evaluated for anatomical obstruction. Consider foreign body aspiration in young children 1 to 4 years of age. Toddlers are especially at risk because of their inherent curiosity, continued oral exploration of objects, and increasing independence and mobility. Foreign body aspiration typically presents with sudden onset of coughing and choking. Definitive diagnosis is made by bronchoscopy; however, an abnormal lateral decubitus radiograph of the chest with a suggestive history is fairly conclusive. Other causes of anatomical obstruction include vascular ring, laryngeal web, tracheobronchomalacia, and tracheal or bronchial stenosis.
Vocal cord dysfunction (VCD) is another condition to consider in the differential diagnosis of wheezing in older children and adolescents; it often presents with intermittent daytime wheezing. VCD results from the unintentional paradoxical adduction (closure) of the vocal cords during inspiration; the exact cause of VCD is unknown. The diagnosis can be made by direct visualization of the vocal cords. Clinical manifestations of vocal cord dysfunction include shortness of breath, especially on exertion, coughing, wheezing, and throat tightness. These manifestations tend to be triggered by exercise.21 VCD can occur concomitantly in children with asthma, but it is important to remember that children suffering from VCD and asthma will not respond completely to asthma therapy.
Infection. Bronchiolitis remains the most common mimic of asthma. Bronchiolitis is a lower respiratory tract infection usually caused by respiratory syncytial virus (RSV) in children less than 2 years of age. Researchers have tried to determine whether bronchiolitis is a precursor for asthma; recent research shows a plausible link between RSV and the development of asthma.22-24 There has been strong evidence from several cohort studies that infections with RSV and rhinovirus during infancy are risk factors for subsequent wheezing in early childhood.23-26 The difficult decision in managing these wheezing infants and young children is whether the patient will need bronchodilators for continued use at home. In a prospective study of 826 subjects followed over the first six years of life, Martinez et al. observed that more than one-third (277 children) had a history of wheezing with respiratory infections at least once in the first three years of life.10 When these children were assessed again at 6 years of age, 164 subjects (60%) had no further episodes of recurrent wheezing. The authors concluded that wheezing in the first three years of life had a fairly benign prognosis.10 Metapneumovirus, adenovirus, influenza, and parainfluenza are other viral respiratory infections that cause airway inflammation that can lead to an asthma exacerbation. Sinusitis and pneumonia can further exacerbate asthma due to the increase in mucus production.
Mechanical. Gastroesophageal reflux disease (GERD) is a difficult diagnosis to make in the infant and young child, especially in the emergency setting. Symptoms that may help differentiate GERD from asthma in infants include arching of the back, frequent or recurrent vomiting, refusing to eat or difficulty eating, abdominal pain, poor growth, and colicky behavior. Older children and adolescents with GERD may have persistent cough. GERD can make the presentation of asthma worse and should be considered in patients with asthma who describe frequent nighttime symptoms.
The exact association between asthma and GERD is not clearly defined, but airway epithelium is extremely sensitive to acid.27 Also, the airway may bronchoconstrict during reflux, which starts the cascade of shortness of breath and airway hyperresponsive as noted above. Since GERD can increase the severity of asthma, it needs to be recognized and treated appropriately. One study of older children with persistent asthma found that effective treatment of GERD resulted in a significant reduction in the need for beta-agonist therapy as well as the dose of daily inhaled corticosteroids.28 Treatment of GERD may include dietary changes such as smaller, thickened feeds or avoidance of heavy meals, and the use of medications.
Cystic fibrosis (CF) is another cause of chronic cough and wheeze. Mechanical obstruction in CF occurs from altered mucus production in the respiratory tract. An increase in airway smooth muscle mass may also play a role.29 Children with the classic presentation of CF may also have gastrointestinal manifestations, including malabsorption and failure to thrive. Consider the diagnosis of CF when symptoms of airway inflammatory disease persist despite treatment with systemic corticosteroids.30 Diagnosis is made by sweat chloride measurement.
Clinical Features
As with any medical condition, history and physical examination are the key components to correctly identify and manage asthma. In the ED setting, a brief physical examination to assess the severity of the exacerbation may come before a complete history is taken. However, for the purpose of this article, the components of the history will be reviewed first.
History. The onset of the current exacerbation needs to be assessed. Ask about specific symptoms during this attack as well as previous exacerbations. Individuals often report similar symptoms with each exacerbation even though the presentation of acute asthma will vary widely from one patient to the next. Determine the duration of symptoms prior to seeking care. It has recently been shown that children with shorter duration of symptoms prior to presentation to the ED often have better clinical outcomes compared to children with several days of symptoms; this is likely due to a faster response to therapy.31,32 Sedik and colleagues demonstrated that children with sudden-onset exacerbations had a shorter stay in the ED and were less likely to be admitted to the hospital when compared to those with longer-onset exacerbations; both groups had a similar asthma severity at triage.31
Identify precipitating factors or triggers such as infections, exercise, or changes in the environment. Additional elements of the social history that should be asked include heating source (i.e., kerosene heater, wood-burning stove, etc.), occupation of the parents and the patient (if applicable), and exposure to allergens that may aggravate asthma. Ask specifically about exposure to environmental tobacco smoke (ETS). Exposure to ETS has been associated with an increased risk of developing asthma.33,34
Document all current medications and the timing of the last dose for each medication. For the current exacerbation, ask about the number of inhaled albuterol treatments in the past hour prior to coming to the ED; also ask about the number of albuterol treatments in the past 24 hours. Recent or current use of systemic steroids should be noted; children who are having an exacerbation of asthma despite being on systemic steroids need special consideration.
Assess compliance with medications, as this plays a big role in the disposition of the patient. Determine how often patients are using their short-acting beta-agonist (SABA) inhalers. Use of more than one SABA inhaler per month or more than three per year indicates inadequate control. Patients who use long-acting beta-agonists (LABAs) typically have moderate to persistent asthma. Determine appropriate use of LABAs; use of LABAs as a rescue medication for an asthma attack is inappropriate. Ask about the frequency of use of inhaled corticosteroids (ICS), if they have been prescribed.
Categorize the severity of the patient's asthma between acute episodes. Asthma can be classified according to severity as mild intermittent, mild persistent, moderate persistent, and severe persistent. The "Rule of Twos" can help distinguish those with intermittent asthma from those with persistent asthma; daily symptoms more than two times a week or nightly symptoms more than two times in one month should be classified as persistent asthma.35 It is important to distinguish between intermittent and persistent asthma because the long-term management is different; ICS should be added to the treatment regimen of any patient classified with persistent asthma, including mild persistent asthma.7
Ask about previous admissions to the hospital and intensive care unit for asthma as part of the past medical history. The patient should also be asked about any previous admissions which required intubation. Frequency of ED and other acute care visits can provide additional clues about severity of disease and compliance. Note any coexisting comorbid conditions such as cardiopulmonary diseases or gastroesophageal reflux, as these conditions may be contributing to the current exacerbation.
If the patient is presenting with an initial episode of wheezing, inquire about symptoms that are consistent with asthma. Ask specifically about other atopic diseases such as food allergies, eczema, and allergic rhinitis; presence of these diseases supports the diagnosis of asthma. Note a family history of asthma, as this is a strong predictor of childhood asthma.8
Physical Examination. Rapidly determine the severity of the episode, including the degree of respiratory distress, as soon as the patient presents to the ED. A child who appears agitated and is struggling to breathe is exhibiting signs of severe respiratory distress. A patient presenting with a severe exacerbation may exhibit decreased or altered mental status with extreme difficulty in breathing; they may even appear hungry for air. Use of all accessory muscles as well as abdominal breathing may be noted. Perfusion may be decreased and the predicted peak flow rate (PEFR), if performed, is less than 50%.
In a moderate exacerbation, the patient may speak in broken sentences with complaints of chest tightness. PEFR will be 50%–70% of the predicted rate; subcostal and intercostal retractions will be present. In a mild exacerbation, the patient will be alert and talkative with good perfusion. PEFR will be 70%–90% of the expected value, and retractions will be minimal or absent.
Obtain and review vital signs immediately. Oxygen saturation, heart rate, respiratory rate, blood pressure, and temperature should be noted. Normal respiratory rates vary considerably by age. For example, tachypnea in an infant is defined as a respiratory rate of more than 60 breaths per minute, whereas in a 6- to 8-year-old, tachypnea is defined as more than 30 breaths per minute.7
Blood pressure should be noted with particular attention paid to any significant changes in the systolic blood pressure with inspiration. Asthma is the most common extra-cardiac cause of pulsus paradoxus; presence of this physical finding in an acute exacerbation is an ominous sign.36 Pulsus paradoxus is measured by having the patient not breathe too deeply; the sphygmomanometer is inflated above the systolic pressure. Peak systolic pressure during expiration is first identified. The cuff is slowly deflated to determine the systolic blood pressure that can be heard during both inspiration and expiration. The accepted upper limit of normal for a fall in systolic blood pressure with inspiration is 10 mmHg; anything above this is considered pulsus paradoxus.36 According to Hartet and colleagues, the degree of pulsus paradoxus can be estimated from a pulse oximetry tracing; they provide additional information on this process in their 1999 article.37
The respiratory system is the primary focus of the examination. A patient with acute asthma will often present with a prolonged expiratory phase and end expiratory wheezes on auscultation. However, there may be a range of findings on auscultation of the lungs. Wheezing may be audible without the use of a stethoscope, or there may be no wheezing audible on auscultation. A patient with extremely poor aeration may not be moving any air; thus wheezing will not be appreciated. The presence of wheezing is not a reliable indicator of airway obstruction; in fact, the absence of wheeze due to severe airway obstruction is known as the "silent chest" and is a worrisome sign.38 Decreased breath sounds could indicate a pneumothorax, and pneumonia could also cause decreased breath sounds or rales. Consider a diagnosis other than asthma if the patient has stridor or inspiratory wheezing. In particular, upper airway manifestations like vocal cord dysfunction or foreign body aspiration should be taken into account. Other elements of the respiratory exam include assessment of accessory muscle use and retractions, nasal flaring and cyanosis.
Assess pulses and perfusion as part of the cardiovascular exam. Presence of a murmur or a gallop rhythm on auscultation of the heart should alert the clinician to underlying cardiac pathology; rales may also be present in instances of pulmonary edema. As mentioned previously, tachycardia may be a side effect of SABA therapy; however, it may also be a sign of hypovolemia. Hydration status should be assessed; patients can become dehydrated from increased losses from the respiratory tract due to tachypnea.
Follow the patient's mental status; both agitation and lethargy may be associated with severe respiratory distress. Decreased mental status likely indicates impending respiratory failure and should be addressed immediately. The ability to speak in complete sentences often indicates a milder level of respiratory distress. A patient who is not able to carry on a conversation because of increased work of breathing should be monitored closely as this is a sign of worsening respiratory distress.
If the diagnosis of asthma has not been previously established, look for signs on the physical exam that would support the diagnosis. Supportive findings on the physical exam that would suggest an atopic phenotype include dry skin, eczema or atopic dermatitis, allergic shiners (dark circles under the eyes), injected conjunctivae, boggy nasal turbinates, nasal discharge, and an "allergic crease" on the bridge of the nose.39
Diagnostic Evaluation
When a child presents to the ED with an exacerbation of asthma, particular attention should be paid to the respiratory rate, accessory muscle use, and level of consciousness to determine next steps. Documentation of oxygen saturation with a noninvasive technique such as pulse oximetry is useful for the initial assessment as well as serial assessments to gauge the effective of treatments.
PEFR should be documented if the patient is able to cooperate. Although children older than 6 years of age should be able to perform a PEFR reliably, a recent study indicated that only 41% of children younger than 6 years with asthma reported ever using a peak flow meter.40 Children younger than 6 years as well as children in considerable distress may not be able to perform PEFR. One study of 1,178 pediatric and adult patients evaluated for asthma in the ED found that PEFR was measured in less than 25% of all subjects. Among the 276 children who were tested, only 6% were younger than 6 years of age; less than half of children younger than 12 years of age were tested.41 Some experts recommend the measurement of lung function using spirometry or PEFR during an exacerbation; however, the feasibility of this in an acute care setting has been questioned.40-43 Use of the PEFR to assess a child using a peak flow meter for the first time during an acute exacerbation should be done with caution. Gorelick and colleagues emphasized that treatment protocols can not rely on the PEFR as the exclusive assessment of severity during an exacerbation. In their study of 456 children from 6 years to 18 years presenting to the ED with acute asthma, only 291 had PEFR measured, and more than one-third of these children did not perform PEFR correctly.42
The use of quantitative end tidal carbon dioxide (ETCO2) has been suggested as an objective, noninvasive way to assess the severity of an asthma exacerbation.44,45 The benefit of ETCO2 is that unlike PEFR, it is effort-independent and can be done in children as young as one year.45 Langhan and colleagues showed that lower ETCO2 values were significantly associated with lower oxygen saturations, higher respiratory rates, and higher pulmonary scores (degree of wheezing, accessory muscle use and respiratory rate).45
Asthma is primarily a clinical diagnosis. Additional testing is not necessary for effective management; however, there are certain situations in which ancillary testing should be considered. It should be emphasized that treatment should not be delayed while waiting for the results of ancillary tests.
Blood tests for a complete blood count (CBC) and serum chemistries are not necessary in the routine management of an asthma exacerbation. Consider obtaining a CBC when the index of suspicion is high for a bacterial etiology as the trigger for the exacerbation. Leukocytosis is a common nonspecific finding in asthma exacerbations; administration of corticosteroids can further increase the number of circulating polymorphonuclear cells. Monitor serum potassium, magnesium, and phosphorus in a patient who is receiving multiple doses of beta-agonists, especially in patients with underlying heart disease where minor electrolyte imbalances can be detrimental. Monitor patients on diuretics for electrolyte imbalances. Obtain an arterial blood gas (ABG) in patients who present in severe respiratory distress and/or have a PEFR < 25% of predicted.7 An ABG should also be obtained when the patient's status is not improving despite standard therapy; increasing hypercarbia or worsening hypoxemia can be indications of impending respiratory failure. Note that a normal pCO2 in a child with marked tachypnea is not reassuring and may indicate CO2 retention from fatigue.
Obtain a blood culture if the patient is febrile, ill-appearing or there is concern for bacteremia or bacterial pneumonia. If the patient is having productive sputum, a respiratory culture may identify an infectious etiology. Viral respiratory cultures may be helpful in determining further management strategies. Consider testing for RSV in children younger than 2 years presenting with their first episode of wheezing during the fall and winter.
Chest radiographs are often normal in children with asthma except for non-specific findings such as hyperinflation and peribronchial thickening. Order a chest radiograph when there is concern for an acute cardiopulmonary process such as pneumothorax, heart failure or pneumonia. A chest radiograph can also be considered for those patients who fail to respond to standard therapy. Chest computed tomography is the preferred study in the detection of bronchiectasis (irreversible dilatation of the peripheral airways) which is associated with cystic fibrosis, aspergillosis, ciliary dyskinesia, and other immune deficiencies.
Management
The cornerstone of managing an acute exacerbation of asthma is to correct hypoxemia and reverse airway obstruction. Oxygen administration should be considered in all moderate to severe exacerbations, regardless of pulse oximetry readings. Oxygen not only increases the partial pressure of arterial oxygen and decreases work of breathing; it has bronchodilatory properties as well.
The pharmacologic mainstays for asthma exacerbations include SABAs and systemic corticosteroids. (Guidelines for common medications used during an exacerbation and their doses can be found in the table "Dosages of Drugs for Astha Exacerbations" in the enclosed Rapid Access Management Guidelines.)
Airway obstruction can be reversed rapidly with the administration of SABAs. Administration of an inhaled SABA should not be delayed if the patient is a known asthmatic or has a history of wheezing in the past with response to beta-agonist therapy. The most common SABA is racemic albuterol; the dose for nebulized treatment is 0.15 mg/kg nebulizer solution. The standard initial dose for children less than five years of age who weigh less than 30 kilograms is 2.5 mg. For children older than five years who weigh more than 30 kilograms, the standard dose is 5 mg per treatment. The onset of action for SABAs is typically five minutes or less. Subsequent doses of SABAs can be given every 15–20 minutes. In the ED, three SABA treatments given over the course of one hour is considered a safe and effective initial therapy.7
The standard method of delivery in administering SABA treatments is via nebulizer; the advantages to using a nebulizer in the ED include administration while the patient is asleep, and the concurrent administration of oxygen or other inhaled medications such as ipratropium bromide.46 However, the use of a metered dose inhaler (MDI) to deliver SABAs has been shown to be as effective as nebulizer for administration. One study in the ED found that four puffs of a SABA via MDI with spacer was as effective as 2.5 mg of a nebulized SABA in young children (mean age < 2 years) presenting to the ED with acute wheezing.47 A recent review of six trials of MDI use in children younger than 5 years of age presenting to the ED with moderate to severe exacerbations found that use of an MDI with a valved holding chamber was more effective than a nebulizer in decreasing hospitalizations.48
Continuous inhalational treatment with SABAs may be more effective than intermittent inhalational treatments for those patients experiencing a significant degree of airway obstruction.49,50 Dosing for continuous nebulized albuterol is 0.5 mg/kg/hour (max dose 25–30 mg/hour). Analysis of eight randomized, controlled trials comparing intermittent versus continuous albuterol nebulizer treatments in a total of 461 patients found that continuous administration of nebulized albuterol was well-tolerated and safe. There was no difference in heart rate, blood pressure or serum potassium between the two groups. Furthermore, patients receiving continuous treatment with albuterol were less likely to need hospitalization (relative risk 0.68, 95% 0.5–0.9).50
Compared to racemic albuterol, which is a 50:50 mixture of the R-albuterol and S-albuterol, levalbuterol is a made up entirely of R-albuterol. The R-albuterol isomer has been promoted as having a much greater binding capacity with the beta-agonist receptors and none of the side effects of S-albuterol.51,52 The theoretical benefits of using levalbuterol in lieu of racemic albuterol have not been definitively proven in the clinical setting. While one study of 482 children ages 1–18 years found a significantly lower rate of hospitalization between patients treated with levalbuterol (36%) versus patients treated with racemic albuterol (45%),53 two subsequent studies in 2005 failed to show any differences in outcome between children treated with levalbuterol versus racemic albuterol.54,55
In severe exacerbations that do not respond to inhaled SABAs, adding inhaled ipratropium bromide may improve response. Ipratropium bromide works by providing additional bronchodilation. Administering inhaled ipratropium bromide concomitantly with a SABA can reduce the need for hospitalization, especially in patients with a significant amount of airway obstruction.56,57
Systemic corticosteroids work by decreasing airway inflammation; they should be considered in all moderate or severe exacerbations and for patients who fail to respond promptly to a SABA. A review of 17 controlled clinical trials of oral corticosteroids for children with acute asthma found that administration of steroids in the ED within one hour of presentation improved clinical outcomes.58,59 Oral corticosteroids are preferred if the patient is able to take medication by mouth; the NAEPP guidelines recommend oral administration over intravenous or intramuscular dosing because it is less invasive.7 (Guidelines regarding dosages by weight can be found in the table "Dosages of Drugs for Astha Exacerbations" in the enclosed Rapid Access Management Guidelines.)
Most patients will respond to the therapies outlined above, especially if SABA therapy and corticosteroids are administered promptly. For severe exacerbations which are not responding to the usual interventions adjunct therapies such as magnesium sulfate or heliox can be tried. Rodrigo and colleagues conducted a systematic review of six studies looking at the use of heliox in adult and pediatric patients presenting to the ED with acute asthma. They found that the current data did not support the use of heliox in adult patients presenting to the ED; there was insufficient data to draw any conclusions on the use of heliox in the pediatric population.60 Recent studies in children have yielded conflicting results. Kim and colleagues compared nebulized albuterol delivered by heliox with nebulized albuterol delivered by oxygen and found a greater degree of clinical improvement in children receiving the heliox mixture.61 Another randomized, controlled trial in children compared albuterol nebulized in heliox versus control and found no clinical benefit from the use of heliox.62 The current NAEPP guidelines recommend that heliox be considered in life-threatening exacerbations as well as severe exacerbations that are not improving after one hour of intensive conventional therapy.7
Although current evidence does not support the routine use of intravenous magnesium sulfate for pediatric patients with acute asthma,63 there does appear to be some benefit in its use in patients presenting with a severe exacerbation. A systematic review of the literature revealed that intravenous magnesium sulfate did in fact reduce hospital admissions in a subset of adult and pediatric patients presenting with severe exacerbations. Furthermore, it was well tolerated in all patients without significant changes in vital signs and no increase in reported side effects.64
At present there is insufficient data to routinely recommend the use of intravenous beta2-agonists (e.g. terbutaline) and intravenous leukotriene receptor agonists (e.g. montelukast). Regarding intravenous terbutaline, Travers and colleagues state that the only indication for its use is when inhaled beta-agonist therapy is not feasible.65 The current NAEPP guidelines state that both intravenous beta2-agonists and intravenous leukotriene receptor agonists may be considered to avoid intubation when all other recommended therapies have been tried.7
In severe exacerbations that are unresponsive to conventional therapy, adjunct therapies such as heliox, magnesium sulfate, and terbutaline may be tried in an attempt to avoid intubation. Noninvasive ventilation such as continuous positive airway pressure is becoming more common and may be an option for patients in moderate respiratory distress who are not in impending respiratory failure.46 However, intubation may be a medical necessity in some situations and once the decision to intubate has been made, the procedure should not be delayed.
Any child who presents with apnea or coma should be intubated immediately. There are no other absolute indications for intubation; however, altered mental status and exhaustion from increased work of breathing are other indicators of impending respiratory failure. Hypercarbia alone should not be used as an indication for intubation. Recognize that intubation of the asthmatic patient is difficult; the procedure itself results in bronchospasm. Complications from intubation and mechanical ventilation include barotrauma and hypotension.
Ketamine, because of its bronchodilatory effects, is the preferred induction agent for intubation in patients with severe asthma;66 however, a clinical benefit in nonintubated patients has not been proven. A recent randomized controlled trial found that ketamine did not provide any additional benefit to the standard regimen for children presenting to the ED with a moderately severe asthma attack. Using the pulmonary index score (range 0–12) developed by Becker to assess clinical outcome, the pulmonary index was 10.3 for the placebo group and 10.5 for the ketamine group. After treatment with albuterol and either placebo or ketamine, the placebo group showed an average decrease in the pulmonary index of 3.6 compared to 3.2 for the ketamine group.67
There is no role for LABAs such as salmeterol in the management of an asthma exacerbation; their delayed onset of action makes them impractical for an acute attack. The use of mucolytics and chest physical therapy are also not recommended for the management of acute asthma, nor are methylxanthines such as aminophylline.7 Studies have shown no proven benefit for adding theophylline to the treatment regimen. The 1992 NAEPP guidelines recommended against the use of methyxanthines for asthma exacerbations and their use dropped significantly. In 1993 it was reported that methylxanthines were used in 20% of all ED visits for asthma. By 1995, methylxanthines were used in less than 0.1% of visits.5
Antibiotics are not necessary in the routine management of an asthma exacerbation; however, pulmonary infections from pneumococcus, Chlamydia, or Mycoplasma can lead to asthma exacerbation. Antibiotics should be added to the treatment regimen when bacterial pneumonia is suspected. Intravenous hydration may be necessary to replace any deficits from insensible losses through the respiratory tract; however, caution must be taken to avoid overhydration because this can worsen the patient's respiratory status.
All patients should be monitored for their response to therapy. There are a variety of criteria which can be used to assess response to therapy during an exacerbation including the patient's subjective response, PEFR if obtained, and pulse oximetry. Pulse oximetry can be used to ascertain initial severity and can also be used as one indicator of response to therapy. Oxygen saturations that remain less than 92% to 94% are often used as predictive of the need for hospitalization.7
Geelhoed and colleagues evaluated the role of initial pulse oximetry reading upon presentation to the ED in determining risk for admission to the hospital or return to the ED with ongoing symptoms after discharge. In a review of 280 pediatric ED visits for acute asthma, they found that pulse oximetry was a reliable outcome predictor; specifically, oxygen saturations of 91% or less were associated with an odds ratio of 35 (CI 11–150) for hospital admission or return ED visit when compared to O2 saturations of 96% or greater.68 These findings are consistent with those of Pollack and colleagues, who found an increase in odds ratio for hospitalization of 2.2 for each 5% decrease in oxygen saturation.41
Initial O2 saturation as a predictor of hospitalization has been studied; when used alone, it was not a clinically useful predictor of admission. A study found that 88% of 1,040 children presented to the ED with SaO2 of 91% or greater on room air. Twenty-three percent of all patients were subsequently admitted. The difference in mean SaO2 between patients admitted and those who were not was 93% and 96% respectively; however, a specific cutoff value for the initial oxygen saturation that would reliably predict which children needed admission was not identified.69
Response to therapy should be gauged by serial assessments of the patient; a single assessment is not reliable. Twaddell and colleagues attempted to determine whether a single assessment of children with acute asthma at presentation to the ED could predict final disposition. Initial assessment based on oxygen saturation, degree of wheezing, and presence of pulsus paradoxus was made of 53 children upon admission to the ED. They predicted that 17 patients would require hospitalization upon presentation to the ED; 15 of these patients were subsequently admitted. However, the authors of the study questioned the utility of the single assessment because almost half of the 53 patients were initially assigned to an indeterminate category in which the investigators were not able to predict the need for hospitalization.70
Many studies have looked at clinical indicators other than lung function to assess the severity of an exacerbation as well as the patient's response to intervention. The pulmonary index score, mentioned earlier, was one of the first clinical scores used to assess pediatric patients with acute asthma in the ED.71 Four components were assessed: respiratory rate, degree of wheezing, inspiratory–expiratory ratio, and use of accessory muscles. Each component was scored on a scale of 0–3, with a maximum score of 12.
Smith and colleagues proposed another pulmonary score to assess the severity of acute asthma, based on respiratory rate, sternocleidomastoid retractions, and degree of wheezing. Each of these components are scored on a scale of 0–3 with a total score ranging from 0–9. A mild exacerbation included total scores of 0–3; moderate exacerbations, 4–6; and severe, 7–9.72 The validity of the pulmonary score was tested in 46 children age 5–17 years; it was found to correlate well with PEFR and served as a good substitute for measuring the severity of asthma in children being managed in an ED. The authors recommended use of the pulmonary score particularly for children too young to perform PEFR and for those patients whose exacerbations were too severe to perform PEFR.
More recently, Gorelick and colleagues developed the Pediatric Asthma Severity Score (PASS) for the evaluation of acute asthma.73 The PASS is a clinical asthma score which can be used in children age 1–18 years of age in an acute clinical setting. The authors describe the PASS as easy to use with good interrater reliability. It is based on three clinical findings: wheezing, prolonged expiration, and work of breathing. The PASS correlates well with pulse oximetry and PEFR. Furthermore it can discriminate between patients who require hospitalization and those who do not.73
Regardless of which score or index is used, patients should be assessed frequently during the ED course. At a minimum, monitor patients after the initial SABA treatment and after three doses of SABA.7 Children should be observed for 30–60 minutes after their last treatment to ensure that they do not relapse. The patient's response to therapy will determine disposition.
Clinical Outcomes and Disposition
A severe asthma exacerbation which is not responding to standard therapy is termed status asthmaticus; this is a life-threatening emergency which can lead to respiratory failure and death. Prompt recognition of status asthmaticus is essential to maximizing therapy to prevent poor outcomes. Drowsiness or altered mental status is an ominous sign and can indicate impending respiratory failure. Other signs of impending respiratory failure include inability to speak, worsening fatigue or tiring out, and a PCO2 of > 42 mmHg.66 Other complications of severe asthma exacerbations that can lead to a sudden deterioration include atelectasis and air leak syndromes such as pneumomediastinum and pneumothorax.
It is important to note that infants are at greater risk of respiratory failure than older children and adults.7 There are fundamental differences in the anatomy and physiology of their lungs. In particular, their ventilation/perfusion characteristics can result in hypoxemia much faster than in adults. Pulse oximetry should be monitored closely. Infants can also progress to respiratory failure more quickly due to air trapping and hypoventilation.7
Certain factors have been associated with fatal asthma; they include age younger than 1 year, past history of severe exacerbations, previous ICU admissions and intubations, and frequent ED visits or hospitalizations for asthma. Two or more hospitalizations in the past year or three or more ED visits in the past year are considered significant. The presence of a comorbid condition such as heart disease or a lack of awareness of airflow obstruction have also been found to be risk factors. Finally, excessive use of SABAs (more than two canisters per month) or recent use of systemic steroids can be risk factors.35,46,66
Approximately 10%–25% of all ED visits for acute asthma will result in hospitalization despite appropriate therapy.5,41,74 Ginde and colleagues reviewed almost 24 million ED visits for asthma and found that of the 63% of visits that were triaged as urgent or emergent, 12% resulted in admission to the hospital.5 Compared to adult patients, a larger percentage of pediatric patients are hospitalized for acute asthma following presentation to the ED. In one study of 1,178 pediatric patients seen in the ED for acute asthma, 23% of patients were hospitalized. This admission rate was likely higher than what might be expected in community EDs because it was conducted in EDs largely located at academic medical centers. The median admission rate by ED site was 20%, with an interquartile range of 11% to 30%.41 Admitted patients were more likely to have been previously hospitalized for asthma, and used ICS in the past month. They were also more likely to have a complication like pneumonia or pneumothorax. Age at diagnosis of asthma, history of ever receiving systemic corticosteroids, recent beta-agonist use, tobacco exposure, and use of ED services did not differ between groups (admitted versus not).41
Although the initial pulse oximetry reading is not a good predictor of the need for hospitalization, an SaO2 of less than 92% after one hour of treatment increases the risk of hospitalization.68 Any child with mental status changes requires admission. If there is concern for noncompliance with the treatment regimen or a lack of awareness on the part of the patient and family regarding the severity of the exacerbation, hospitalization is also recommended. (See Table 1.)
 |
All patients who can be discharged from the ED should receive asthma education, appropriate medications to manage their exacerbation, and a concrete plan for follow-up. Asthma teaching can be done by a physician or nurse. The following topics should be discussed: use of inhalers and a peak flow meter (if the patient is older than 6 years of age), the patient's asthma action plan, and a review of asthma triggers. Each patient should leave with clear, written instructions regarding the proper use and dosage of their medication. A sample discharge form with patient instructions is available in the current NAEPP guidelines.7
Review medications and dosages needed to treat the current episode as well as which medications the patient will continue to need once the exacerbation has resolved. Patients should be discharged from the ED with a 5- to 10-day course of oral corticosteroids to prevent relapse. If noncompliance with oral steroids is a concern, a single dose of intramuscular (IM) dexamethasone can be considered instead of the course of oral steroids.75,76 Gordon and colleagues found no difference in outcomes at four days after ED discharge in young children (younger than 7 years of age) taking a five-day course of oral prednisolone versus those who received an IM dose of dexamethasone at discharge.76
Identify children who present to the ED with suboptimal control of their asthma. This may be difficult, especially in children who exclusively receive care in the ED and do not have a medical home. For the majority of patients presenting to the ED with an asthma exacerbation, a failure of their long-term management has occurred. Inquire about the presence of daily and nightly symptoms between exacerbations. If not already on daily controller medication such as ICS, children with symptoms of persistent asthma would benefit from a prescription for ICS in addition to their SABA and short course of systemic steroids.77 The NAEPP guidelines encourage physicians to discharge patients from the ED with a one- to two-month supply of ICS if they meet the criteria for any category of persistent asthma.7 A prescription for ICS in addition to oral steroids at discharge from the ED can improve patients' symptoms, reduce relapses, and improve the likelihood of continued use of an ICS as a daily controller medication for children with persistent asthma.77-79
There are several choices for ICS; the recent NAEPP guidelines include a table of the various options with comparative doses for each.7 Fluticasone is a commonly prescribed ICS for the daily control of persistent asthma. Dosages are expressed as the amount of drug actually delivered to the patient (actuator dose); fluticasone MDIs are available in 44 micrograms, 110 micrograms, and 220 micrograms per puff. A good starting dose for children 0–11 years of age with persistent asthma is 176 micrograms daily. The total daily dose should be divided in half for twice-daily dosing. Instructing patients on the use of a spacer or valved holding chamber with their MDI is important; children younger than 4 years of age will benefit from a spacer with a facemask.
Review asthma triggers with the patient and family, particularly the control of environmental factors which may trigger subsequent exacerbations. Counsel about the risks of ETS exposure. Teach the patient and caregivers to recognize worsening signs of asthma so that there are clear guidelines of when to seek medical care again.
Follow-up with a primary care physician is essential even if the patient is symptom free upon discharge from the ED. Although the NAEPP guidelines have suggested follow-up within five days, it would be prudent to have children treated for a moderate to severe exacerbation follow up within 24 hours. Factors associated with an increased likelihood of follow-up after an asthma exacerbation include a recent hospitalization for asthma, the parent's assessment that the child's asthma is "very severe," more than one ED visit in the previous year for asthma, and current daily use of ICS80
Emphasize the importance of follow-up with the patient so that future exacerbations can be minimized. Ongoing asthma education, which includes a review of medication dosages as well as proper technique for using inhalers, can be discussed at these follow-up visits. Ideally these visits should take place in the patient's medical home and build upon key points reviewed prior to discharge from the ED. Education of the pediatric patient with asthma has been shown to reduce the number of hospitalizations and ED visits.81 Assistance with scheduling the follow-up appointment for the patient in the ED has been shown to increase the likelihood that they will keep their appointment.82
Conclusions
Some clinicians do not endorse the use of clinical practice guidelines in an ED setting, citing inefficiency as a major obstacle; however, clinical practice guidelines for asthma have been used successfully in the pediatric ED for acute exacerbations. Scribano and colleagues assessed compliance with the 1997 NAEPP guidelines for managing an asthma exacerbation in urban pediatric ED settings and found complete adherence in 68% of the cases in children older than 6 years. Furthermore, when the requirement for obtaining a PEFR on all patients older than 6 years of age was dropped, adherence to the recommendations increased to 83%.40
The benefits of ED protocols for managing acute asthma are many. Use of pre-printed order sheets for asthma exacerbations have been shown to reduce the number of return visits to the ED for asthma symptoms within 72 hours.43 ED protocols have resulted in an increase in the use of objective measures such as PEFR, use of effective therapy per national guidelines, healthcare delivery that is cost-effective, and a reduction in hospital admission rates.83 Ly and colleagues reviewed 141 pediatric visits for asthma in an academic ED and demonstrated that implementation of a standard protocol improved patient care. Protocol guidelines were met in all patients regarding pulse oximetry monitoring and in most patients regarding the use of SABAs. Furthermore, over 90% of patients received asthma education from a nurse or physician prior to discharge. One-third of patients received training on the use of asthma devices such as a peak flow meter or an MDI.84 Specific areas of improvement included more frequent measurement of PEFR in children older than 6 years and an increase in prescriptions for ICS at discharge for children with persistent asthma.84
Although the first NAEPP guidelines were released more than 15 years ago, studies have continued to indicate there is still room for improvement in adopting the recommendations for managing acute asthma. While the use of SABAs is universal in most cases of acute asthma, the appropriate use of other available medications as well as guidance on discharge planning and education in the ED are not standardized. Use of standardized protocols in the ED based on consensus recommendations will improve outcomes for children presenting with asthma exacerbations. ED physicians can improve the outcomes of their patients with asthma by following evidence-based guidelines. The 2007 NAEPP guidelines have up-to-date information for managing asthma exacerbations in the ED, and adoption of these guidelines into standard practice can further reduce morbidity and mortality of patients with asthma.
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